The Pro12Ala substitution in the peroxisome proliferator activated receptor gamma 2 is associated with an insulin-sensitive phenotype in families with familial combined hyperlipidemia and in nondiabetic elderly subjects withdyslipidemia

Dyslipidemias and insulin resistance often present simultaneously, as in fa milial combined hyperlipidemia (FCHL), and therefore may have a common gene tic background. In our previous study the Pro12Ala substitution of peroxiso me proliferator receptor gamma 2 (PPAR gamma 2) associated with insulin sen sitivity, low body mass index (BMI) and high-density lipoprotein (HDL) chol esterol levels. In this study, we investigated the role of this substitutio n in dyslipidemias. Therefore, 228 nondiabetic members of FCHL families and 866 nondiabetic elderly subjects with (n = 217) and without dyslipidemia ( n = 649) were genotyped. The allele frequencies of the Pro12Ala substitutio n did not differ between elderly subjects with or without dyslipidemia or 2 7 probands with FCHL. However. this substitution was associated with low fa sting insulin levels both in FCHL family members (P = 0.036 adjusted for ge nder and age) and elderly subjects with dyslipidemia (P = 0.050) but not in elderly subjects without dyslipidemia (P = 0.080). In addition, the Ala12 allele of PPAR gamma 2 was associated with low BMI (P = 0.034) and low tota l triglycerides (P = 0.027), and increased HDL-cholesterol (P < 0.001) in e lderly subjects with dyslipidemia (n = 299) but not among any other study g roups. We conclude that the Ala12 isoform of PPAR gamma 2 ameliorates the i nsulin resistance and unfavorable lipid and lipoprotein profiles in FCHL an d hyperlipidemic elderly subjects. (C) 2000 Elsevier Science Ireland Ltd. A ll rights reserved.